Unknown

Dataset Information

0

Aminothiazoles inhibit osteoclastogenesis and PGE2 production in LPS-stimulated co-cultures of periodontal ligament and RAW 264.7 cells, and RANKL-mediated osteoclastogenesis and bone resorption in PBMCs.


ABSTRACT: Inflammatory mediator prostaglandin E2 (PGE2 ) contributes to bone resorption in several inflammatory conditions including periodontitis. The terminal enzyme, microsomal prostaglandin E synthase-1 (mPGES-1) regulating PGE2 synthesis is a promising therapeutic target to reduce inflammatory bone loss. The aim of this study was to investigate effects of mPGES-1 inhibitors, aminothiazoles TH-848 and TH-644, on PGE2 production and osteoclastogenesis in co-cultures of periodontal ligament (PDL) and osteoclast progenitor cells RAW 264.7, stimulated by lipopolysaccharide (LPS), and bone resorption in RANKL-mediated peripheral blood mononuclear cells (PBMCs). PDL and RAW 264.7 cells were cultured separately or co-cultured and treated with LPS alone or in combination with aminothiazoles. Multinucleated cells stained positively for tartrate-resistant acid phosphatase (TRAP) were scored as osteoclast-like cells. Levels of PGE2 , osteoprotegerin (OPG) and interleukin-6, as well as mRNA expression of mPGES-1, OPG and RANKL were analysed in PDL cells. PBMCs were treated with RANKL alone or in combination with aminothiazoles. TRAP-positive multinucleated cells were analysed and bone resorption was measured by the CTX-I assay. Aminothiazoles reduced LPS-stimulated osteoclast-like cell formation both in co-cultures and in RAW 264.7 cells. Additionally, aminothiazoles inhibited PGE2 production in LPS-stimulated cultures, but did not affect LPS-induced mPGES-1, OPG or RANKL mRNA expression in PDL cells. In PBMCs, inhibitors decreased both osteoclast differentiation and bone resorption. In conclusion, aminothiazoles reduced the formation of osteoclast-like cells and decreased the production of PGE2 in co-cultures as well as single-cell cultures. Furthermore, these compounds inhibited RANKL-induced bone resorption and differentiation of PBMCs, suggesting these inhibitors for future treatment of inflammatory bone loss such as periodontitis.

SUBMITTER: Kats A 

PROVIDER: S-EPMC6349150 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Aminothiazoles inhibit osteoclastogenesis and PGE<sub>2</sub> production in LPS-stimulated co-cultures of periodontal ligament and RAW 264.7 cells, and RANKL-mediated osteoclastogenesis and bone resorption in PBMCs.

Kats Anna A   Gerasimcik Natalija N   Näreoja Tuomas T   Nederberg Jonas J   Grenlöv Simon S   Lagnöhed Ekaterina E   Desai Suchita S   Andersson Göran G   Yucel-Lindberg Tülay T  

Journal of cellular and molecular medicine 20181201 2


Inflammatory mediator prostaglandin E<sub>2</sub> (PGE<sub>2</sub> ) contributes to bone resorption in several inflammatory conditions including periodontitis. The terminal enzyme, microsomal prostaglandin E synthase-1 (mPGES-1) regulating PGE<sub>2</sub> synthesis is a promising therapeutic target to reduce inflammatory bone loss. The aim of this study was to investigate effects of mPGES-1 inhibitors, aminothiazoles TH-848 and TH-644, on PGE<sub>2</sub> production and osteoclastogenesis in co-c  ...[more]

Similar Datasets

| S-EPMC4882984 | biostudies-literature
| S-EPMC6723172 | biostudies-literature
| S-EPMC7504656 | biostudies-literature
| S-EPMC4052347 | biostudies-literature
| S-EPMC3419183 | biostudies-literature
| S-EPMC5601052 | biostudies-literature
| S-EPMC7915339 | biostudies-literature
| S-EPMC9235393 | biostudies-literature
| S-EPMC6688344 | biostudies-literature
| S-EPMC5871721 | biostudies-literature